title: Plasma membrane tension orchestrates membrane trafficking, cytoskeletal remodeling, and biochemical signaling during phagocytosis.
abstract: Phagocytes clear the body of undesirable particles such as infectious agents and debris. To extend pseudopods over the surface of targeted particles during engulfment, cells must change shape through extensive membrane and cytoskeleton remodeling. We observed that pseudopod extension occurred in two phases. In the first phase, pseudopods extended rapidly, with actin polymerization pushing the plasma membrane forward. The second phase occurred once the membrane area from preexisting reservoirs was depleted, leading to increased membrane tension. Increased tension directly altered the small Rho GTPase Rac1, 3'-phosphoinositide, and cytoskeletal organization. Furthermore, it activated exocytosis of vesicles containing GPI-anchored proteins, increasing membrane area and phagocytosis efficiency for large particles. We thus propose that, during phagocytosis, membrane remodeling, cytoskeletal organization, and biochemical signaling are orchestrated by the mechanical signal of membrane tension. These results put a simple mechanical signal at the heart of understanding immunological responses.
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Masters
authors.forename: Bruno
authors.initials: B
authors.lastname: Pontes
authors.forename: Virgile
authors.initials: V
authors.lastname: Viasnoff
authors.forename: You
authors.initials: Y
authors.lastname: Li
authors.forename: Nils C
authors.initials: NC
authors.lastname: Gauthier
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins; D001696:Biomechanical Phenomena; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000276:immunology*; D003599:Cytoskeleton / Q000502:physiology; D031541:Fluorescence Resonance Energy Transfer; D006639:Histidine / Q000031:analogs & derivatives / Q000378:metabolism; D008164:Luminescent Proteins; D051379:Mice; D018613:Microscopy, Confocal / Q000379:methods; D052898:Optical Tweezers; D010587:Phagocytosis / Q000276:immunology*; D011554:Pseudopodia / Q000276:immunology*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D001426:Bacterial Proteins; D008164:Luminescent Proteins; C054562:yellow fluorescent protein, Bacteria; D006639:Histidine; D020830:rac1 GTP-Binding Protein; C005436:phosphohistidine
keywords: Rho GTPases; frustrated phagocytosis; immunology; phagocytic cell; traffic